A Study of TQ05105 in Patients With Chronic Graft Versus Host Disease

A Single Group, Open-Label, Multicenter ,Phase Ib/II Clinical Trials of TQ05105 Tablet in Patients With Glucocorticoid Refractory and Dependent Moderate to Severe Chronic Graft Versus Host Disease (cGVHD).

This study was a single arm, open label, multicenter phase Ib / II trial in subjects with glucocorticoid refractory / dependent moderate to severe cGVHD.The trial consisted of two phases: phase I for the dose exploration and phase II for the extension study.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Graft Versus Host Disease
• Intervention / Treatment: Drug: TQ05105 Tablet

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: He Huang, Doctor; Phone Number: 0571-87236703; Email: hehuangyu@126.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510280
      • Zhujiang hospital of southern medical university
    • Guangzhou, Guangdong, China, 511457
      • Guangzhou First People's Hospital
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Tongji Medical College of HUST
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of hematology & blood diseases hospital, chinese academy of medical sciences & peking union medical college
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Understood and signed an informed consent form.
• ≥18 years old, Karnofsky Performance Scale of ≥60, life expectancy ≥ 6 months.
• Has received allogeneic hematopoietic stem cell transplantation (alloSCT).
• Clinically diagnosed moderate to severe cGVHD according to NIH Consensus Criteria.
• Has received systemic or topical corticosteroids therapy and confirmed steroid-refractory/dependent cGVHD according to NIH Consensus Criteria.
• Has received at least 1 lines of therapy for cGVHD.
• Adequate laboratory indicators.
• No pregnant or breastfeeding women, and a negative pregnancy test.

Exclusion Criteria:

• Has active acute GVHD.
• Has previously failed to respond to JAK inhibitors for GVHD, or who had used JAK inhibitors within 4 weeks before the first administration.
• Has uncontrollable active infections or infections requiring systematic treatment within 7 days before the first administration.
• Development of other basic diseases.
• Has malignant tumors within 3 years.
• Has multiple factors affecting oral medication.
• Has substance abuse or a psychotic disorder.
• Has severe and / or uncontrolled disease.
• Allergic to drugs or its constituents.
• Has participated in any other clinical trials within 4 weeks before first administration.
• According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQ05105 Tablet; TQ05105 tablet 10mg given orally, twice daily in 28-cycle.	Drug: TQ05105 Tablet; TQ05105 tablet is a Janus Kinase (JAK) inhibitor, which can inhibit the abnormal activation of JAK 2-V617F mutation, thereby inhibiting the sustained abnormal activation of JAK / STAT pathway.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Tolerable Dose (MTD)	If dose limiting toxicity (DLT) occurs in 2 or more subjects in a given dose group, the dose level in the previous dose group is considered MTD. (Patients in phase Ib)	Baseline up to 4 weeks
Recommended phase II dose (RP2D)	Recommended dose for phase II (Patients in phase Ib)	Baseline up to 4 weeks
Best Overall Response Rate (BOR)	Percentage of participants achieving complete response (CR) and partial response (PR). (Patients in phase II)	Baseline up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure Free Survival (FFS)	Defined as absence of relapse, death, or need for additional systemic immunosuppressant cGVHD therapy.	Baseline up to 12 months
Overall Response Rate (ORR)	Percentage of participants achieving complete response (CR) and partial response (PR) during the study according to the cGVHD NIH Consensus Criteria.	Baseline up to 52 weeks
Duration of Response (DOR)	DOR defined as time from earliest date of disease response to earliest date of disease progression.	Baseline up to 96 weeks
Overall survival (OS)	OS defined as the time from randomization to the time of death from any cause.	Baseline up to death event, up to 5 years.
Non-relapse mortality (NRM)	Defined as the date of first dose to the date of death from non hematologic disease recurrence / progression	Baseline up to 96 weeks
Changes in glucocorticoid dose	The reduction in glucocorticoid requirement would be regarded as an effect of the trial drug.	Baseline up to 96 weeks
Changes in symptom burden	Evaluate changes in symptom burden as measured by the Lee Symptom Scale. A change of 7 points on the Lee Symptom Scale will be considered clinically significant and relates to improvement in quality of life.	Baseline up to 96 weeks
Maximum plasma concentration (Cmax)	Cmax is the maximum plasma concentration of TQ05105 or its metabolite(s).	Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 1; Pre-dose of day 3,day5, day 6 ;Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 7.
Time to reach maximum plasma concentration (Tmax)	To characterize the pharmacokinetics of TQ05105 by assessment of time to reach maximum plasma concentration.	Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 1; Pre-dose of day 3,day5, day 6 ;Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 7.
Area under the plasma concentration time curve (AUC0-t)	To characterize the pharmacokinetics of TQ05105 by assessment of area under the plasma concentration time curve from zero to infinity.	Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 1; Pre-dose of day 3,day5, day 6 ;Pre-dose, 5, 15 , 30 minutes, 1 , 2 , 3 , 6, 8, 11 hours post-dose of day 7.
Incidence rate of adverse event	The occurrence rate of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs) assessed based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.	Baseline up to 96 weeks.

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: June 26, 2021
• First Posted (Actual): June 29, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: TQ05105-Ib/II-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No